Effects and mechanisms of AKR1C3 inducing doxorubicin resistance in breast cancer
10.11665/j.issn.1000-5048.20210313
- VernacularTitle:醛酮还原酶AKR1C3介导乳腺癌阿霉素耐药的作用及其机制
- Author:
Kaizhen WANG
1
;
Wanwan YANG
;
Shengyao XU
;
Qinglong GUO
;
Li ZHAO
Author Information
1. 中国药科大学基础医学与临床药学学院
- Publication Type:Journal Article
- Keywords:
aldo-keto reductase;
AKR1C3;
β-catenin;
breast cancer;
DOX resistance
- From:
Journal of China Pharmaceutical University
2021;52(3):352-360
- CountryChina
- Language:Chinese
-
Abstract:
To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.
